The project is concerned with investigations of cholinergic synapses and transmission at the periphery (ganglia and neuromyal junction) and in the CNS, of the effects of drugs of various types on cholinergic transmission, and of the relations between cholinergic and other neurotransmitter systems. This year, we investigated the mechanisms of facilitation and inhibition at the mammalian including human skeletal neuromyal junction. Methyl-isobutyl-xanthine (MIX), a congener of the xanthine compound oxtryphylline, previously shown by us to be effective in certain cases of myasthenia gravis, exhibited unusual facilitatory nerve terminal actions, exemplified in marked increase of MEPP frequency, quantal content and probability of release. Furthermore, this compound may exert certain facilitatory postsynaptic actions. As more potent in animal tests than oxtryphylline and as possibly less prone to produce side actions, MIX may offer some therapeutic possibilities. Other facilitatory mechanisms studied this year concerned "short term" facilitation which can be demonstrated with paired stimuli. This facilitation as that due to MIX may be based on presynaptic mechanisms; its relation to Ca to the 2nd power ion and conversion into depression by d-tubocurarine were demonstrated. Our studies concerned also the measurement of membrane characteristics and of MEPPs of human (non-myasthenic) intercostal preparations. The Re values were obtained; their multi-model distribution may reflect the fact that the human intercostal muscle contains several types of fibers as indicated by histochemical analysis. Finally, certain episodes of myasthenia-type myopathies induced by drugs and possibly allergenic substances were investigated. Another study involved the denervated sympathetic ganglion of the rabbit. Our earlier findings of the desensitization of the nicotinic site and sensitization of the muscarinic site following denervation were confirmed and expanded. The data indicate that these changes do not involve membrane characteristics and excitability or the receptor-ACh affinity and complexing; possibly, denervation induces changes in the density or area of the muscarinic and nicotinic receptors. Further investigations of the affect of increased levels of ACh on other neurotransmitters or transmitter-like substances were carried out. As in the case of catecholamine levels (cf. earlier (Text Truncated - Exceeds Capacity)